Changes in epithelial renewal may be important in the pathogenesis of mucosal disease of the upper gastrointestinal tract. We have shown in rats that aspirin ingestion over four weeks stimulates epithelial proliferation in the stomach, whereas ingestion of hydrocortisone sodium succinate for four weeks depresses gastric epithelial proliferation. Further, oral administration of the carcinogen N-methyl-N'-nitro-N-nitrosoguandidine (MNNG) stimulated gastroduodenal epithelial proliferation and caused marked villous blunting and crypt hypertrophy in duodenal mucosa of rats. MNNF treatment also resulted in a downward expansion of the proliferative zone in antral and fundic mucosa. We propose to continue to study the effects of steroids on epithelial renewal by determining whether the initial effect of steroids is on inhibition of the rate of cell loss from the mucosal surface of the stomach or duodenum (i.e., the villous tips). We also will continue to study the effects of various agents on gastroduodenal epithelial proliferation to include ethanol and cimetidine. Finally, we will, by use of organ culture methods, study epithelial proliferation in biopsy material from humans with peptic disease or who are exposed to potential ulcerogens.